Juanita L Merchant

Interests

Research

GI physiology Gastrointestinal cancersTranscriptional control mechanismsMouse models of GI physiology and cancerHelicobacter pylori and gastric cancer

Teaching

GI physiology Gastrointestinal cancersTranscriptional control mechanismsMouse models of GI physiology and cancerHelicobacter pylori and gastric cancer

Courses

Scholarly Contributions

Books

• Merchant, J. (2016). Recapitulating human gastric cancer pathogenesis: Experimental models of gastric cancer.
• Merchant, J. (2012). Physiology of the Gastrointestinal Tract.
• Merchant, J. (2006). Physiology of the Gastrointestinal Tract.

Chapters

• Merchant, J. (2018). Transcription and Epigenetic Regulation. In Physiology of the Gastrointestinal Tract: Sixth Edition.
• Merchant, J. (2010). Hedgehog signaling in gastric physiology and cancer. In Progress in Molecular Biology and Translational Science.
• Merchant, J. (2009). Atrophy and altered mesenchymal-epithelial signaling preceding gastric cancer. In The Biology of Gastric Cancers.
• Merchant, J. (2005). 4 role of p53 and ZBP-89 in hepatocellular carcinoma. In Handbook of Immunohistochemistry and in Situ Hybridization of Human Carcinomas.

Journals/Publications

• Merchant, J. L. (2022). Moving Up a NOTCH: Defining the Stem Cell Niche in the Gastric Antrum. Cellular and molecular gastroenterology and hepatology, 13(1), 339-340.
• Chakrabarti, J., Koh, V., Steele, N., Hawkins, J., Ito, Y., Merchant, J. L., Wang, J., Helmrath, M. A., Ahmad, S. A., So, J. B., Yong, W. P., & Zavros, Y. (2021). Disruption of Her2-Induced PD-L1 Inhibits Tumor Cell Immune Evasion in Patient-Derived Gastric Cancer Organoids. Cancers, 13(24).
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  (1) Background: The expression of programmed death-ligand 1 (PD-L1), which interacts with programmed cell death protein 1 (PD-1) on cytotoxic T lymphocytes (CTLs), enables tumors to escape immunosurveillance. The PD-1/PD-L1 interaction results in the inhibition of CTL proliferation, and effector function, thus promoting tumor cell evasion from immunosurveillance and cancer persistence. Despite 40% of gastric cancer patients exhibiting PD-L1 expression, only a small subset of patients responds to immunotherapy. Human epidermal growth factor receptor2 (HER2) is one of the critical regulators of several solid tumors, including metastatic gastric cancer. Although half of PD-L1-positive gastric tumors co-express HER2, crosstalk between HER2 and PD-1/PD-L1 in gastric cancer remains undetermined. (2) Methods: Human gastric cancer organoids (huTGOs) were generated from biopsied or resected tissues and co-cultured with CTLs and myeloid-derived suppressor cells (MDSCs). Digital Spatial Profiling (DSP) was performed on FFPE tissue microarrays of numerous gastric cancer patients to examine the protein expression of immune markers. (3) Results: Knockdown of HER2 in PD-L1/HER2-positive huTGOs led to a concomitant decrease in PD-L1 expression. Similarly, in huTGOs/immune cell co-cultures, PD-L1 expression decreased in huTGOs and was correlated with an increase in CTL proliferation which enhanced huTGO death. Treatment with Nivolumab exhibited similar effects. However, a combinatorial treatment with Mubritinib and Nivolumab was unable to inhibit HER2 expression in co-cultures containing MDSCs. (4) Conclusions: Our study suggested that co-expression of HER2 and PD-L1 may contribute to tumor cell immune evasion. In addition, autologous organoid/immune cell co-cultures can be exploited to effectively screen responses to a combination of anti-HER2 and immunotherapy to tailor treatment for gastric cancer patients.
• Ding, L., Sontz, E. A., Saqui-Salces, M., & Merchant, J. L. (2021). Interleukin-1β Suppresses Gastrin via Primary Cilia and Induces Antral Hyperplasia. Cellular and molecular gastroenterology and hepatology, 11(5), 1251-1266.
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  Helicobacter pylori infection in humans typically begins with colonization of the gastric antrum. The initial Th1 response occasionally coincides with an increase in gastrin secretion. Subsequently, the gastritis segues to chronic atrophic gastritis, metaplasia, dysplasia and distal gastric cancer. Despite these well characterized clinical events, the link between inflammatory cytokines and non-cardia gastric cancer remains difficult to study in mouse models. Prior studies have demonstrated that overexpression of the Hedgehog (HH) effector GLI2 induces loss of gastrin (atrophy) and antral hyperplasia. To determine the link between specific cytokines, HH signaling and pre-neoplastic changes in the gastric antrum.
• Farshidpour, M., Ahmed, M., Junna, S., & Merchant, J. L. (2021). Myeloid-derived suppressor cells in gastrointestinal cancers: A systemic review. World journal of gastrointestinal oncology, 13(1), 1-11.
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  Gastrointestinal (GI) cancers are one of the most common malignancies worldwide, with high rates of morbidity and mortality. Myeloid-derived suppressor cells (MDSCs) are major components of the tumor microenvironment (TME). MDSCs facilitate the transformation of premalignant cells and play roles in tumor growth and metastasis. Moreover, in patients with GI malignancies, MDSCs can lead to the suppression of T cells and natural killer cells. Accordingly, a better understanding of the role and mechanism of action of MDSCs in the TME will aid in the development of novel immune-targeted therapies.
• Koh, V., Chakrabarti, J., Torvund, M., Steele, N., Hawkins, J. A., Ito, Y., Wang, J., Helmrath, M. A., Merchant, J. L., Ahmed, S. A., Shabbir, A., Yan So, J. B., Yong, W. P., & Zavros, Y. (2021). Hedgehog transcriptional effector GLI mediates mTOR-Induced PD-L1 expression in gastric cancer organoids. Cancer letters, 518, 59-71.
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  Tumors evade immune surveillance by expressing Programmed Death-Ligand 1 (PD-L1), subsequently inhibiting CD8 cytotoxic T lymphocyte function. Response of gastric cancer to immunotherapy is relatively low. Our laboratory has reported that Helicobacter pylori-induced PD-L1 expression within the gastric epithelium is mediated by the Hedgehog (Hh) signaling pathway. The PI3K/AKT/mTOR pathway is activated in gastric cancer and may have immunomodulatory potential. We hypothesize that Hh signaling mediates mTOR-induced PD-L1 expression. Patient-derived organoids (PDOs) were generated from gastric biopsies and resected tumor tissues. Autologous organoid/immune cell co-cultures were used to study the immunosuppressive function of MDSCs. NanoString Digital Spatial Profiling (DSP) of immune-related protein markers using FFPE slide-mounted tissues from gastric cancer patients was performed. DSP analysis showed infiltration of immunosuppressive MDSCs expressing Arg1, CD66b, VISTA and IDO1 within cancer tissues. Orthotopic transplantation of patient derived organoids (PDOs) resulted in the engraftment of organoids and the development of histology similar to that observed in the patient's tumor tissue. PDO/immune cell co-cultures revealed that PD-L1-expressing organoids were unresponsive to nivolumab in vitro in the presence of PMN-MDSCs. Depletion of PMN-MDSCs within these co-cultures sensitized the organoids to anti-PD-1/PD-L1-induced cancer cell death. Rapamycin decreased phosphorylated S6K, Gli2 and PD-L1 expression in PDO/immune cell co-cultures. Transcriptional regulation of PD-L1 by GLI1 and GLI2 was blocked by rapamycin. In conclusion, the PDO/immune cell co-cultures may be used to study immunosuppressive MDSC function within the gastric tumor microenvironment. The mTOR signaling pathway mediates GLI-induced PD-L1 expression in gastric cancer.
• Merchant, J. (2020). Interleukin-1β Suppresses Gastrin via Primary Cilia and Induces Antral Hyperplasia. Cell Mol Gastroenterol Hepatol.
• Rico, K., Duan, S., Pandey, R. L., Chen, Y., Chakrabarti, J. T., Starr, J., Zavros, Y., Else, T., Katona, B. W., Metz, D. C., & Merchant, J. L. (2021). Genome analysis identifies differences in the transcriptional targets of duodenal versus pancreatic neuroendocrine tumours. BMJ open gastroenterology, 8(1).
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  Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) encompass a diverse group of neoplasms that vary in their secretory products and in their location within the gastrointestinal tract. Their prevalence in the USA is increasing among all adult age groups.
• Merchant, J. (2020). A brief review of liver injury in patients with Corona Virus Disease-19 during the pandemic.. Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology.
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  The novel coronavirus Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) infection has been mostly leading to respiratory distress syndrome, but liver injury has also been documented. The mechanism of liver injury is limited and poorly understood. However, the hepatic injury could be due to a consequence of systemic inflammatory response, viral infection of hepatocytes, or as a result of intensive care treatment or drug toxicity. Based on the current studies, this review article emphasizes on the demographic and potential mechanisms of Corona Virus Disease (COVID)-19-related liver dysfunction.
• Merchant, J. (2020). Interleukin-1β Suppresses Gastrin via Primary Cilia and Induces Antral Hyperplasia.. Cellular and molecular gastroenterology and hepatology.
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  BackgroundHelicobacter pylori infection in humans typically begins with colonization of the gastric antrum. The initial Th1 response occasionally coincides with an increase in gastrin secretion. Subsequently, the gastritis segues to chronic atrophic gastritis, metaplasia, dysplasia and distal gastric cancer. Despite these well characterized clinical events, the link between inflammatory cytokines and non-cardia gastric cancer remains difficult to study in mouse models. Prior studies have demonstrated that overexpression of the Hedgehog (HH) effector GLI2 induces loss of gastrin (atrophy) and antral hyperplasia.AimTo determine the link between specific cytokines, HH signaling and pre-neoplastic changes in the gastric antrum.MethodsMouse lines were created to conditionally direct IL-1β or IFNγ to the antrum using the Gastrin-CreERT2 and Tet activator. Primary cilia, which transduces HH signaling, on G cells were disrupted by deleting the ciliary motor protein KIF3a. Phenotypic changes were assessed by histology and western blots. A subclone of GLUTag enteroendocrine cells selected for gastrin expression and the presence of primary cilia was treated with recombinant SHH, IL-1β or IFNγ with or without kif3a siRNA.ResultsIFNγ increased gastrin and induced antral hyperplasia. However, antral expression of IL-1β suppressed tissue and serum gastrin, while also inducing antral hyperplasia. IFNγ treatment of GLUTAg cells suppressed GLI2 and induced gastrin, without affecting cilia length. By contrast, IL-1β treatment doubled primary cilia length, induced GLI2 and suppressed gastrin gene expression. Knocking down kif3a in GLUTAg cells mitigated SHH or IL-1β suppression of gastrin.ConclusionOverexpression of IL-1β in the antrum was sufficient to induce antral hyperplasia coincident with suppression of gastrin via primary cilia.
• Merchant, J. (2020). MiR130b from Schlafen4+ MDSCs stimulates epithelial proliferation and correlates with preneoplastic changes prior to gastric cancer.. Gut.
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  The myeloid differentiation factor Schlafen4 (Slfn4) marks a subset of myeloid-derived suppressor cells (MDSCs) in the stomach during Helicobacter-induced spasmolytic polypeptide-expressing metaplasia (SPEM). OBJECTIVE:To identify the gene products expressed by Slfn4+-MDSCs and to determine how they promote SPEM. DESIGN:We performed transcriptome analyses for both coding genes (mRNA by RNA-Seq) and non-coding genes (microRNAs using NanoString nCounter) using flow-sorted SLFN4+ and SLFN4- cells from Helicobacter-infected mice exhibiting metaplasia at 6 months postinfection. Thioglycollate-elicited myeloid cells from the peritoneum were cultured and treated with IFNα to induce the T cell suppressor phenotype, expression of MIR130b and SLFN4. MIR130b expression in human gastric tissue including gastric cancer and patient sera was determined by qPCR and in situ hybridisation. Knockdown of MiR130b in vivo in Helicobacter-infected mice was performed using Invivofectamine. Organoids from primary gastric cancers were used to generate xenografts. ChIP assay and Western blots were performed to demonstrate NFκb p65 activation by MIR130b. RESULTS:MicroRNA analysis identified an increase in MiR130b in gastric SLFN4+ cells. Moreover, MIR130b colocalised with SLFN12L, a human homologue of SLFN4, in gastric cancers. MiR130b was required for the T-cell suppressor phenotype exhibited by the SLFN4+ cells and promoted Helicobacter-induced metaplasia. Treating gastric organoids with the MIR130b mimic induced epithelial cell proliferation and promoted xenograft tumour growth. CONCLUSION:Taken together, MiR130b plays an essential role in MDSC function and supports metaplastic transformation.
• Merchant, J. (2020). Murine- and Human-Derived Autologous Organoid/Immune Cell Co-Cultures as Pre-Clinical Models of Pancreatic Ductal Adenocarcinoma.. Cancers.
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  Purpose: Pancreatic ductal adenocarcinoma (PDAC) has the lowest five-year survival rate of all cancers in the United States. Programmed death 1 receptor (PD-1)-programmed death ligand 1 (PD-L1) immune checkpoint inhibition has been unsuccessful in clinical trials. Myeloid-derived suppressor cells (MDSCs) are known to block anti-tumor CD8+ T cell immune responses in various cancers including pancreas. This has led us to our objective that was to develop a clinically relevant in vitro organoid model to specifically target mechanisms that deplete MDSCs as a therapeutic strategy for PDAC. Method: Murine and human pancreatic ductal adenocarcinoma (PDAC) autologous organoid/immune cell co-cultures were used to test whether PDAC can be effectively treated with combinatorial therapy involving PD-1 inhibition and MDSC depletion. Results: Murine in vivo orthotopic and in vitro organoid/immune cell co-culture models demonstrated that polymorphonuclear (PMN)-MDSCs promoted tumor growth and suppressed cytotoxic T lymphocyte (CTL) proliferation, leading to diminished efficacy of checkpoint inhibition. Mouse- and human-derived organoid/immune cell co-cultures revealed that PD-L1-expressing organoids were unresponsive to nivolumab in vitro in the presence of PMN-MDSCs. Depletion of arginase 1-expressing PMN-MDSCs within these co-cultures rendered the organoids susceptible to anti-PD-1/PD-L1-induced cancer cell death. Conclusions: Here we use mouse- and human-derived autologous pancreatic cancer organoid/immune cell co-cultures to demonstrate that elevated infiltration of polymorphonuclear (PMN)-MDSCs within the PDAC tumor microenvironment inhibit T cell effector function, regardless of PD-1/PD-L1 inhibition. We present a pre-clinical model that may predict the efficacy of targeted therapies to improve the outcome of patients with this aggressive and otherwise unpredictable malignancy.
• Merchant, J. (2020). ZBP-89 negatively regulates self-renewal of liver cancer stem cells via suppression of Notch1 signaling pathway. Cancer Letters.
• Merchant, J. (2019). Generation of organoids from mouse extrahepatic bile ducts. Journal of Visualized Experiments.
• Merchant, J. (2019). Reduced efficacy of low FODMAPs diet in patients with IBS-D carrying sucrase-isomaltase (SI) hypomorphic variants.. Gut.
• Merchant, J. (2019). ZFP148 (Zinc-Finger Protein 148) Binds Cooperatively with NF-1 (Neurofibromin 1) to Inhibit Smooth Muscle Marker Gene Expression during Abdominal Aortic Aneurysm Formation. Arteriosclerosis, Thrombosis, and Vascular Biology.
• Merchant, J. (2018). Hedgehog Signaling Modulates Interleukin-33-Dependent Extrahepatic Bile Duct Cell Proliferation in Mice.. Hepatology communications.
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  Hedgehog (HH) signaling participates in hepatobiliary repair after injury and is activated in patients with cholangiopathies. Cholangiopathies are associated with bile duct (BD) hyperplasia, including expansion of peribiliary glands, the niche for biliary progenitor cells. The inflammation-associated cytokine interleukin (IL)-33 is also up-regulated in cholangiopathies, including cholangiocarcinoma. We hypothesized that HH signaling synergizes with IL-33 in acute inflammation-induced BD hyperplasia. We measured extrahepatic BD (EHBD) thickness and cell proliferation with and without an IL-33 challenge in wild-type mice, mice overexpressing Sonic HH (pCMV-Shh), and mice with loss of the HH pathway effector glioma-associated oncogene 1 (Gli1lacZ/lacZ ). LacZ reporter mice were used to map the expression of HH effector genes in mouse EHBDs. An EHBD organoid (BDO) system was developed to study biliary progenitor cells in vitro. EHBDs from the HH overexpressing pCMV-Shh mice showed increased epithelial cell proliferation and hyperplasia when challenged with IL-33. In Gli1lacZ/lacZ mice, we observed a decreased proliferative response to IL-33 and decreased expression of Il6. The HH ligands Shh and Indian HH (Ihh) were expressed in epithelial cells, whereas the transcriptional effectors Gli1, Gli2, and Gli3 and the HH receptor Patched1 (Ptch1) were expressed in stromal cells, as assessed by in situ hybridization and lacZ reporter mice. Although BDO cells lacked canonical HH signaling, they expressed the IL-33 receptor suppression of tumorigenicity 2. Accordingly, IL-33 treatment directly induced BDO cell proliferation in a nuclear factor κB-dependent manner. Conclusion: HH ligand overexpression enhances EHBD epithelial cell proliferation induced by IL-33. This proproliferative synergism of HH and IL-33 involves crosstalk between HH ligand-producing epithelial cells and HH-responding stromal cells.
• Merchant, J. (2018). Indian Hedgehog Suppresses Intestinal Inflammation. Cellular and Molecular Gastroenterology and Hepatology.
• Merchant, J. (2018). Isolation of enteric glial cells from the submucosa and lamina propria of the adult mouse. Journal of Visualized Experiments.
• Merchant, J. (2018). Mature enteroendocrine cells contribute to basal and pathological stem cell dynamics in the small intestine. American Journal of Physiology - Gastrointestinal and Liver Physiology.
• Merchant, J. (2018). Parietal Cell Death by Cytokines. Cellular and Molecular Gastroenterology and Hepatology.
• Merchant, J. (2017). A Summary of the 2016 James W. Freston Conference of the American Gastroenterological Association: Intestinal Metaplasia in the Esophagus and Stomach: Origins, Differences, Similarities and Significance. Gastroenterology.
• Merchant, J. (2017). Deletion of Men1 and somatostatin induces hypergastrinemia and gastric carcinoids. Gut.
• Merchant, J. (2017). Gastric Acid Secretion from Parietal Cells Is Mediated by a Ca²⁺ Efflux Channel in the Tubulovesicle. Developmental Cell.
• Merchant, J. (2017). Gastrin Induces Nuclear Export and Proteasome Degradation of Menin in Enteric Glial Cells. Gastroenterology.
• Merchant, J. (2017). Hedgehog Signaling Links Chronic Inflammation to Gastric Cancer Precursor Lesions. Cellular and Molecular Gastroenterology and Hepatology.
• Merchant, J. (2017). Pathophysiology of Gastric NETs: Role of Gastrin and Menin. Current Gastroenterology Reports.
• Merchant, J. (2017). SCHLAFEN 5 expression correlates with intestinal metaplasia that progresses to gastric cancer. Journal of Gastroenterology.
• Merchant, J. (2017). Weight gain in mice on a high caloric diet and chronically treated with omeprazole depends on sex and genetic background. American Journal of Physiology - Gastrointestinal and Liver Physiology.
• Merchant, J. (2017). ZBP-89 function in colonic stem cells and during butyrateinduced senescence. Oncotarget.
• Merchant, J. (2016). Invasive mouse gastric adenocarcinomas arising from Lgr5+ stem cells are dependent on crosstalk between the Hedgehog/GLI2 and mTOR pathways. Oncotarget.
• Merchant, J. (2016). NF-κB mediated transcription of DARPP-32 prevents Helicobacter pylori-induced cell death. Gut.
• Merchant, J. (2016). Schlafen 4-expressing myeloid-derived suppressor cells are induced during murine gastric metaplasia. Journal of Clinical Investigation.
• Merchant, J. (2016). Transcription factor ZBP-89 drives a feedforward loop of β-catenin expression in colorectal cancer. Cancer Research.
• Grasberger, H., Gao, J., Nagao-Kitamoto, H., Kitamoto, S., Zhang, M., Kamada, N., Eaton, K. A., El-Zaatari, M., Shreiner, A. B., Merchant, J. L., Owyang, C., & Kao, J. Y. (2015). Increased Expression of DUOX2 Is an Epithelial Response to Mucosal Dysbiosis Required for Immune Homeostasis in Mouse Intestine. GASTROENTEROLOGY, 149(7), 1849-1859.
• Merchant, J. (2015). Increased Expression of DUOX2 Is an Epithelial Response to Mucosal Dysbiosis Required for Immune Homeostasis in Mouse Intestine. Gastroenterology.
• Merchant, J. (2015). Pilot study of Biomarkers for predicting effectiveness of ramosetron in diarrhea-predominant irritable bowel syndrome: Expression of S100A10 and polymorphisms of TPH1. Neurogastroenterology and Motility.
• Merchant, J. (2014). Inhibition of Hedgehog signaling in the gastrointestinal tract: Targeting the cancer microenvironment. Cancer Treatment Reviews.
• Merchant, J. (2014). Stress hematopoiesis is regulated by the Krüppel-like transcription factor ZBP-89. Stem Cells.
• El-Zaatari, M., Kao, J. Y., Tessier, A., Bai, L., Hayes, M. M., Fontaine, C., Eaton, K. A., & Merchant, J. L. (2013). Gli1 Deletion Prevents Helicobacter-Induced Gastric Metaplasia and Expansion of Myeloid Cell Subsets. PLOS ONE, 8(3).
• Essien, B. E., Grasberger, H., Romain, R. D., Law, D. J., Veniaminova, N. A., Saqui-Salces, M., El-Zaatari, M., Tessier, A., Hayes, M. M., Yang, A. C., & Merchant, J. L. (2013). ZBP-89 Regulates Expression of Tryptophan Hydroxylase I and Mucosal Defense Against Salmonella Typhimurium in Mice. GASTROENTEROLOGY, 144(7), 1466-U254.
• Grasberger, H., Chang, L., Shih, W., Presson, A. P., Sayuk, G. S., Newberry, R. D., Karagiannides, I., Pothoulakis, C., Mayer, E., & Merchant, J. L. (2013). Identification of a Functional TPH1 Polymorphism Associated With Irritable Bowel Syndrome Bowel Habit Subtypes. AMERICAN JOURNAL OF GASTROENTEROLOGY, 108(11), 1766-1774.
• Grasberger, H., El-Zaatari, M., Dang, D. T., & Merchant, J. L. (2013). Dual Oxidases Control Release of Hydrogen Peroxide by the Gastric Epithelium to Prevent Helicobacter felis Infection and Inflammation in Mice. GASTROENTEROLOGY, 145(5), 1045-1054.
• Merchant, J. (2013). Dual oxidases control release of hydrogen peroxide by the gastric epithelium to prevent helicobacter felis infection and inflammation in mice. Gastroenterology.
• Merchant, J. (2013). Epigenetic upregulation of Bak by ZBP-89 inhibits the growth of hepatocellular carcinoma. Biochimica et Biophysica Acta - Molecular Cell Research.
• Merchant, J. (2013). Gli1 Deletion Prevents Helicobacter-Induced Gastric Metaplasia and Expansion of Myeloid Cell Subsets. PLoS ONE.
• Merchant, J. (2013). Identification of a functional TPH1 polymorphism associated with irritable bowel syndrome bowel habit subtypes. American Journal of Gastroenterology.
• Merchant, J. (2013). ZBP-89 regulates expression of tryptophan hydroxylase i and mucosal defense against salmonella typhimurium in mice. Gastroenterology.
• Berndt, B. E., Zhang, M., Owyang, S. Y., Cole, T. S., Wang, T. W., Luther, J., Veniaminova, N. A., Merchant, J. L., Chen, C., Huffnagle, G. B., & Kao, J. Y. (2012). Butyrate increases IL-23 production by stimulated dendritic cells. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 303(12), G1384-G1392.
• Merchant, J. (2012). A high-fat diet regulates gastrin and acid secretion through primary cilia. FASEB Journal.
• Merchant, J. (2012). Butyrate increases IL-23 production by stimulated dendritic cells. American Journal of Physiology - Gastrointestinal and Liver Physiology.
• Merchant, J. (2012). Conditional deletion of menin results in antral G cell hyperplasia and hypergastrinemia. American Journal of Physiology - Gastrointestinal and Liver Physiology.
• Merchant, J. (2012). Hedgehog signalling in gut development, physiology and cancer. JOURNAL OF PHYSIOLOGY-LONDON, 590(3), 421-432.
• Merchant, J. (2012). Hedgehog signalling in gut development, physiology and cancer. Journal of Physiology.
• Merchant, J. (2012). IFNγ contributes to the development of gastric epithelial cell metaplasia in Huntingtin interacting protein 1 related (Hip1r)-deficient mice. Laboratory Investigation.
• Merchant, J. (2012). Inflammation and Gli2 Suppress Gastrin Gene Expression in a Murine Model of Antral Hyperplasia. PLoS ONE.
• Merchant, J. (2012). Interaction between ZBP-89 and p53 mutants and its contribution to effects of HDACi on hepatocellular carcinoma. Cell Cycle.
• Merchant, J. (2012). Plasma Shh levels reduced in pancreatic cancer patients. Pancreas.
• Merchant, J. (2012). The same pocket in menin binds both MLL and JUND but has opposite effects on transcription. Nature.
• Merchant, J. (2012). Transgenic expression of interferon-γ in mouse stomach leads to inflammation, metaplasia, and dysplasia. American Journal of Pathology.
• Saqui-Salces, M., Dowdle, W. E., Reiter, J. F., & Merchant, J. L. (2012). A high-fat diet regulates gastrin and acid secretion through primary cilia. FASEB JOURNAL, 26(8), 3127-3139.
• Syu, L., El-Zaatari, M., Eaton, K. A., Liu, Z., Tetarbe, M., Keeley, T. M., Pero, J., Ferris, J., Wilbert, D., Kaatz, A., Zheng, X., Qiao, X., Grachtchouk, M., Gumucio, D. L., Merchant, J. L., Samuelson, L. C., & Dlugosz, A. A. (2012). Transgenic Expression of Interferon-gamma in Mouse Stomach Leads to Inflammation, Metaplasia, and Dysplasia. AMERICAN JOURNAL OF PATHOLOGY, 181(6), 2114-2125.
• Merchant, J. (2011). Gastric tuft cells express DCLK1 and are expanded in hyperplasia. Histochemistry and Cell Biology.
• Merchant, J. (2011). Menin and JunD regulate gastrin gene expression through proximal DNA elements. American Journal of Physiology - Gastrointestinal and Liver Physiology.
• Merchant, J. (2011). ZBP-89 enhances Bak expression and causes apoptosis in hepatocellular carcinoma cells. Biochimica et Biophysica Acta - Molecular Cell Research.
• Merchant, J. (2010). Bone morphogenetic protein signaling regulates gastric epithelial cell development and proliferation in mice. Gastroenterology.
• Merchant, J. (2010). Clogged up. Efforts to train more minority doctors remain stalled as population diversifies.. Modern healthcare.
• Merchant, J. (2010). Hedgehog Is an Anti-Inflammatory Epithelial Signal for the Intestinal Lamina Propria. Gastroenterology.
• Merchant, J. (2010). Hedgehog signaling and gastrointestinal cancer. Biochimica et Biophysica Acta - Molecular Cell Research.
• Merchant, J. (2010). Helicobacter pylori induction of the gastrin promoter through GC-rich DNA elements. Helicobacter.
• Merchant, J. (2010). Interleukin-1β Promotes Gastric Atrophy Through Suppression of Sonic Hedgehog. Gastroenterology.
• Merchant, J. (2010). Intracellular calcium release and protein kinase c activation stimulate sonic hedgehog gene expression during gastric acid secretion. Gastroenterology.
• Merchant, J. (2010). Reply. Gastroenterology.
• Merchant, J. (2010). Underrepresentation of Underrepresented Minorities in Academic Medicine: The Need to Enhance the Pipeline and the Pipe. Gastroenterology.
• Merchant, J. L., & Omary, M. B. (2010). Underrepresentation of Underrepresented Minorities in Academic Medicine: The Need to Enhance the Pipeline and the Pipe. GASTROENTEROLOGY, 138(1), 19-26.
• Saqui-Salces, M., & Merchant, J. L. (2010). Hedgehog signaling and gastrointestinal cancer. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1803(7), 786-795.
• Shinohara, M., Mao, M., Keeley, T. M., El-Zaatari, M., Lee, H., Eaton, K. A., Samuelson, L. C., Merchant, J. L., Goldenring, J. R., & Todisco, A. (2010). Bone Morphogenetic Protein Signaling Regulates Gastric Epithelial Cell Development and Proliferation in Mice. GASTROENTEROLOGY, 139(6), 2050-U349.
• Waghray, M., Zavros, Y., Saqui-Salces, M., El-Zaatari, M., Alamelumangapuram, C. B., Todisco, A., Eaton, K. A., & Merchant, J. L. (2010). Interleukin-1 beta Promotes Gastric Atrophy Through Suppression of Sonic Hedgehog. GASTROENTEROLOGY, 138(2), 562-U202.
• Zacharias, W. J., Li, X., Madison, B. B., Kretovich, K., Kao, J. Y., Merchant, J. L., & Gumucio, D. L. (2010). Hedgehog Is an Anti-Inflammatory Epithelial Signal for the Intestinal Lamina Propria. GASTROENTEROLOGY, 138(7), 2368-U226.
• Kolterud, A., Kolterud, A., Grosse, A. S., Grosse, A. S., Zacharias, W. J., Zacharias, W. J., Walton, K. D., Walton, K. D., Kretovich, K. E., Kretovich, K. E., Madison, B. B., Madison, B. B., Waghray, M., Waghray, M., Ferris, J. E., Ferris, J. E., Hu, C., Hu, C., Merchant, J. L., , Merchant, J. L., et al. (2009). Paracrine Hedgehog Signaling in Stomach and Intestine: New Roles for Hedgehog in Gastrointestinal Patterning. GASTROENTEROLOGY, 137(2), 618-628.
• Merchant, J. (2009). Paracrine Hedgehog Signaling in Stomach and Intestine: New Roles for Hedgehog in Gastrointestinal Patterning. Gastroenterology.
• Merchant, J. (2009). Sonic hedgehog in gastric physiology and neoplastic transformation: Friend or foe?. Current Opinion in Endocrinology, Diabetes and Obesity.
• Merchant, J. (2009). ZBP-89 reduces the cell death threshold in hepatocellular carcinoma cells by increasing caspase-6 and S phase cell cycle arrest. Cancer Letters.
• Jain, R. N., Al-Menhaii, A. A., Keeley, T. M., Ren, J., EI-Zaatari, M., Chen, X., Merchant, J. L., Ross, T. S., Chew, C. S., & Samuelson, L. C. (2008). Hip1r is expressed in gastric parietal cells and is required for tubulovesicle formation and cell survival in mice. JOURNAL OF CLINICAL INVESTIGATION, 118(7), 2459-2470.
• Merchant, J. (2008). Gastrin transactivates the chromogranin A gene through MEK-1/ERK- and PKC-dependent phosphorylation of Sp1 and CREB. Cellular Signalling.
• Merchant, J. (2008). Hip 1r is expressed in gastric parietal cells and is required for tubulovesicle formation and cell survival in mice. Journal of Clinical Investigation.
• Merchant, J. (2008). Induction of follistatin precedes gastric transformation in gastrin deficient mice. Biochemical and Biophysical Research Communications.
• Merchant, J. (2008). Regulated expression of the human gastrin gene in mice. Regulatory Peptides.
• Merchant, J. (2008). Somatostatin stimulates menin gene expression by inhibiting protein kinase A. American Journal of Physiology - Gastrointestinal and Liver Physiology.
• Merchant, J. (2008). Tissue stem cells and cancer stem cells: Potential implications for gastric cancer. Panminerva Medica.
• Merchant, J. (2008). What lurks beneath: IL-11, via Stat3, promotes inflammation-associated gastric tumorigenesis. Journal of Clinical Investigation.
• Bai, L., & Merchant, J. L. (2007). Role for CITED2, a CBP/p300 interacting protein, in colon cancer cell invasion. FEBS LETTERS, 581(30), 5904-5910.
• Chupreta, S., Brevig, H., Bai, L., Merchant, J. L., & Iniguez-Lluhi, J. A. (2007). Sumoylation-dependent control of homotypic and heterotypic synergy by the kruppel-type zinc finger protein ZBP-89. JOURNAL OF BIOLOGICAL CHEMISTRY, 282(50), 36155-36166.
• Merchant, J. (2007). A role for CITED2, a CBP/p300 interacting protein, in colon cancer cell invasion. FEBS Letters.
• Merchant, J. (2007). ATM phosphorylates ZBP-89 at Ser202 to potentiate p21^waf1 induction by butyrate. Biochemical and Biophysical Research Communications.
• Merchant, J. (2007). H pylori infection causes chronic pancreatitis in Mongolian gerbils. World Journal of Gastroenterology.
• Merchant, J. (2007). Prospective Identification of a Multilineage Progenitor in Murine Stomach Epithelium. Gastroenterology.
• Merchant, J. (2007). Re-expression of sonic hedgehog and reduction of CDX2 after Helicobacter pylori eradication prior to incomplete intestinal metaplasia. International Journal of Cancer.
• Merchant, J. (2007). Reduced pepsin A processing of sonic hedgehog in parietal cells precedes gastric atrophy and transformation. Journal of Biological Chemistry.
• Merchant, J. (2007). Sumoylation-dependent control of homotypic and heterotypic synergy by the Krüppel-type zinc finger protein ZBP-89. Journal of Biological Chemistry.
• Merchant, J. (2007). Tales from the crypts: Regulatory peptides and cytokines in gastrointestinal homeostasis and disease. Journal of Clinical Investigation.
• Qiao, X. T., Ziel, J. W., Mckimpson, W., Madison, B. B., Todisco, A., Merchant, J. L., Samuelson, L. C., & Gumucio, D. L. (2007). Prospective identification of a multilineage progenitor in murine stomach epithelium. GASTROENTEROLOGY, 133(6), 1989-1998.
• Shiotani, A., Uedo, N., Iishi, H., Tatsuta, M., Ishiguro, S., Nakae, Y., Kamada, T., Haruma, K., & Merchant, J. L. (2007). Re-expression of sonic hedgehog and reduction of CDX2 after Helicobacter pylori eradication prior to incomplete intestinal metaplasia. INTERNATIONAL JOURNAL OF CANCER, 121(6), 1182-1189.
• Zavros, Y., Waghray, M., Tessier, A., Bai, L., Todisco, A., Gumucio, D. L., Samuelson, L. C., Dlugosz, A., & Merchant, J. L. (2007). Reduced pepsin a processing of sonic hedgehog in parietal cells precedes gastric atrophy and transformation. JOURNAL OF BIOLOGICAL CHEMISTRY, 282(46), 33265-33274.
• Kao, J. Y., Rathinavelu, S., Eaton, K. A., Bai, L., Zavros, Y., Takami, M., Pierzchala, A., & Merchant, J. L. (2006). Helicobacter pylori-secreted factors inhibit dendritic cell IL-12 secretion: a mechanism of ineffective host defense. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 291(1), G73-G81.
• Law, D. J., Labut, E. M., & Merchant, J. L. (2006). Intestinal overexpression of ZNF148 suppresses Apc(Min)/+ neoplasia. MAMMALIAN GENOME, 17(10), 999-1004.
• Merchant, J. (2006). An isoform of ZBP-89 predisposes the colon to colitis. Nucleic Acids Research.
• Merchant, J. (2006). Helicobacter pylori-induced atrophic gastritis progressing to gastric cancer exhibits sonic hedgehog loss and aberrant CDX2 expression. Alimentary Pharmacology and Therapeutics.
• Merchant, J. (2006). Helicobacter pylori-secreted factors inhibit dendritic cell IL-12 secretion: A mechanism of ineffective host defense. American Journal of Physiology - Gastrointestinal and Liver Physiology.
• Merchant, J. (2006). Identification of zinc finger binding protein 89 (ZBP-89) as a transcriptional activator for a major bovine growth hormone receptor promoter. Molecular and Cellular Endocrinology.
• Merchant, J. (2006). Inhibition of growth hormone receptor gene expression by saturated fatty acids: Role of krüppel-like zinc finger factor, ZBP-89. Molecular Endocrinology.
• Merchant, J. (2006). Intestinal alkaline phosphatase gene expression is activated by ZBP-89. American Journal of Physiology - Gastrointestinal and Liver Physiology.
• Merchant, J. (2006). Intestinal overexpression of ZNF148 suppresses Apc^Min/+ neoplasia. Mammalian Genome.
• Merchant, J. (2006). Parietal cell hyperstimulation and autoimmune gastritis in cholera toxin transgenic mice. American Journal of Physiology - Gastrointestinal and Liver Physiology.
• Merchant, J. (2006). Recruitment of Ataxia-Telangiectasia Mutated to the p21^waf1 Promoter by ZBP-89 Plays a Role in Mucosal Protection. Gastroenterology.
• Merchant, J. (2006). Somatostatin inhibits dendritic cell responsiveness to Helicobacter pylori. Regulatory Peptides.
• Merchant, J. (2006). p53 mutants suppress ZBP-89 function. Anticancer Research.
• Merchant, J. (2005). Chronic gastritis in the hypochlorhydric gastrin-deficient mouse progresses to adenocarcinoma. Oncogene.
• Merchant, J. (2005). Epithelial cell turnover in relation to ongoing damage of the gastric mucosa in patients with early gastric cancer: increase of cell proliferation in paramalignant lesions.. Journal of gastroenterology.
• Merchant, J. (2005). Evidence that loss of sonic hedgehog is an indicator of Helicobater pylori-induced atrophic gastritis progressing to gastric cancer. American Journal of Gastroenterology.
• Merchant, J. (2005). Helicobacter pylori cag-type IV secretion system facilitates corpus colonization to induce precancerous conditions in mongolian gerbils. Gastroenterology.
• Merchant, J. (2005). Helicobacter pylori outer membrane protein 18 (Hp1125) induces dendritic cell maturation and function. Helicobacter.
• Merchant, J. (2005). Helicobacter-induced intestinal metaplasia in the stomach correlates with Elk-1 and serum response factor induction of villin. Journal of Biological Chemistry.
• Merchant, J. (2005). Inflammation, atrophy, gastric cancer: Connecting the molecular dots. Gastroenterology.
• Merchant, J. (2005). Interferon gamma induction of gastric mucous neck cell hypertrophy. Laboratory Investigation.
• Merchant, J. (2005). Modulating the cytokine response to treat Helicobacter gastritis. Biochemical Pharmacology.
• Merchant, J. (2005). Regulation and function of the sonic hedgehog signal transduction pathway in isolated gastric parietal cells. Journal of Biological Chemistry.
• Merchant, J. (2005). The Epstein-Barr virus protein BMRF1 activates gastrin transcription. Journal of Virology.
• Merchant, J. L., Shiotani, A., Iishi, H., Ishiguro, S., Tatsuta, M., & Nakae, Y. (2005). Epithelial cell turnover in relation to ongoing damage of the gastric mucosa in patients with early gastric cancer: increase of cell proliferation in paramalignant lesions. Journal of Gastroenterology, 40(4), 337-44. doi:10.1007/s00535-004-1549-9
• Merchant, J. (2004). Inflammation and Cancer III. Somatostatin and the innate immune system. American Journal of Physiology - Gastrointestinal and Liver Physiology.
• Merchant, J. (2004). Kinetic profiles of p300 occupancy in vivo predict common of promoter structure and coactivator recruitment. Proceedings of the National Academy of Sciences of the United States of America.
• Merchant, J. (2004). ZBP-89-induced apoptosis is p53-independent and requires JNK. Cell Death and Differentiation.
• Merchant, J. (2003). A model for integrative study of human gastric acid secretion. Journal of Applied Physiology.
• Merchant, J. (2003). Acinetobacter lwoffii infection and gastritis. Microbes and Infection.
• Merchant, J. (2003). Mutation of p53 in recurrent hepatocellular carcinoma and its association with the expression of ZBP-89. American Journal of Pathology.
• Merchant, J. (2003). Transcription factor ZBP-89 is required for STAT1 constitutive expression. Nucleic Acids Research.
• Merchant, J. (2003). Treatment of Helicobacter gastritis with IL-4 requires somatostatin. Proceedings of the National Academy of Sciences of the United States of America.
• Merchant, J. (2003). ZBP-89 mediates butyrate regulation of gene expression. Journal of Nutrition.
• Merchant, J. (2002). Gastritis and hypergastrinemia due to Acinetobacter lwoffii in mice. Infection and Immunity.
• Merchant, J. (2002). Genetic or chemical hypochlorhydria is associated with inflammation that modulates parietal and G-cell populations in mice. Gastroenterology.
• Merchant, J. (2002). Hypergastrinemia in response to gastric inflammation suppresses somatostatin. American Journal of Physiology - Gastrointestinal and Liver Physiology.
• Merchant, J. (2002). Regulation of epithelial cell growth by ZBP-89: Potential relevance in pancreatic cancer. International Journal of Gastrointestinal Cancer.
• Merchant, J. (2001). Retinoic acid (RA) receptor transcriptional activation correlates with inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase (ODC) activity by retinoids: A potential role for trans-RA-induced ZBP-89 in ODC inhibition. International Journal of Cancer.
• Merchant, J. (2001). TNF-α and interleukin 1 activate gastrin gene expression via MAPK- and PKC-dependent mechanisms. American Journal of Physiology - Gastrointestinal and Liver Physiology.
• Merchant, J. (2001). VacA pores as portable portals for urea. Journal of Clinical Investigation.
• Merchant, J. (2001). ZBP-89 promotes growth arrest through stabilization of p53. Molecular and Cellular Biology.
• Merchant, J. (2001). ZBP-89, Sp1, and Nuclear Factor-κB Regulate Epithelial Neutrophil-activating Peptide-78 Gene Expression in Caco-2 Human Colonic Epithelial Cells. Journal of Biological Chemistry.
• Merchant, J. (2000). An OmpA-like protein from Acinetobacter spp. stimulates gastrin and interleukin-8 promoters. Infection and Immunity.
• Merchant, J. (2000). EGF receptor activation of the human gastrin gene: A tale of two zinc finger transcription factor families. Keio Journal of Medicine.
• Merchant, J. (2000). EGF stimulates gastrin promoter through activation of Sp1 kinase activity. American Journal of Physiology - Cell Physiology.
• Merchant, J. (2000). The zinc finger repressor, ZBP-89, binds to the silencer element of the human vimentin gene and complexes with the transcriptional activator, Sp1. Journal of Biological Chemistry.
• Merchant, J. (2000). Transcription factor ZBP-89 cooperates with histone acetyltransferase p300 during butyrate activation of p21(waf1) transcription in human cells. Journal of Biological Chemistry.
• Merchant, J. (2000). Use of flow cytometry to quantify mouse gastric epithelial cell populations. Digestive Diseases and Sciences.
• Merchant, J. (1999). Sp1 phosphorylation by Erk 2 stimulates DNA binding. Biochemical and Biophysical Research Communications.
• Merchant, J. (1999). ZBP-99 defines a conserved family of transcription factors and regulates ornithine decarboxylase gene expression. Biochemical and Biophysical Research Communications.
• Merchant, J. (1998). The human ZBP-89 homolog, located at chromosome 3q21, represses gastrin gene expression. Mammalian Genome.
• Merchant, J. (1998). Transcription factor ZBP-89 regulates the activity of the ornithine decarboxylase promoter. Journal of Biological Chemistry.
• Merchant, J. (1997). EGF receptor activation stimulates endogenous gastrin gene expression in canine G cells and human gastric cell cultures. Journal of Clinical Investigation.
• Merchant, J. (1997). Epidermal growth factor and okadaic acid stimulate Sp1 proteolysis. Journal of Biological Chemistry.
• Merchant, J. (1997). Gastrin regulates the human histidine decarboxylase promoter through an AP-1-dependent mechanism. American Journal of Physiology - Gastrointestinal and Liver Physiology.
• Merchant, J. (1997). Overexpression of ZBP-89, a zinc finger DNA binding protein, in gastric cancer. Biochemical and Biophysical Research Communications.
• Merchant, J. (1997). RAP1-like binding activity in islet cells corresponds to members of the Sp1 family of transcription factors. FEBS Letters.
• Merchant, J. (1997). Transient transcriptional activation of gastrin during sodium butyrate- induced differentiation of islet cells. Regulatory Peptides.
• Merchant, J. (1997). ZBP-89, a Kruppel-type zinc finger protein, inhibits cell proliferation. Biochemical and Biophysical Research Communications.
• Merchant, J. (1996). Fos is required for EGF stimulation of the gastrin promoter. American Journal of Physiology - Gastrointestinal and Liver Physiology.
• Merchant, J. (1996). ZBP-89, a kruppel-like zinc finger protein, inhibits epidermal growth factor induction of the gastrin promoter. Molecular and Cellular Biology.
• Merchant, J. (1995). Epidermal growth factor stimulation of the human gastrin promoter requires Sp1. Journal of Biological Chemistry.
• Merchant, J. (1995). Sp1 Affinity for GC-Rich Elements Correlates with Ornithine Decarboxylase Promoter Activity. Biochemical and Biophysical Research Communications.
• Merchant, J. (1995). cAMP regulates gastrin gene expression. American Journal of Physiology - Gastrointestinal and Liver Physiology.
• Merchant, J. (1992). Identification of a cis-regulatory element mediating somatostatin inhibition of epidermal growth factor-stimulated gastrin gene transcription. Molecular Endocrinology.
• Merchant, J. (1991). A GC-rich element confers epidermal growth factor responsiveness to transcription from the gastrin promoter. Molecular and Cellular Biology.
• Merchant, J. (1991). Stimulation of gastrin gene transcription by epidermal growth factor/TGFα and inhibition by somatostatin-feedforward and feedback controls on gastrin synthesis to prevent mucosal ulceration by gastrin acid secretion. Fernstrom Foundation Series.
• Merchant, J. (1989). Regulation of the gastrin promoter by epidermal growth factor and neuropeptides. Proceedings of the National Academy of Sciences of the United States of America.
• Merchant, J. (1987). Characterization and use of polyclonal antibody to Na⁺, K⁺‐ATPase: Immunocytochemical localization in salt glands of the duck. Cell Biochemistry and Function.
• Merchant, J. (1985). Correlation of Na+,K+-ATPase content and plasma membrane surface area in adapted and de-adapted salt glands of ducklings.. Journal of cell science.
• Merchant, J. (1977). 3-Hydroxy-3-methylglutaryl coenzyme A reductase in isolated villous and crypt cells of the rat ileum. Journal of Lipid Research.